WO2012085912A2 - Procédé et système d'imagerie d'un os et/ou de diagnostic de l'état d'un os à partir d'une image volumique reconstruite - Google Patents

Procédé et système d'imagerie d'un os et/ou de diagnostic de l'état d'un os à partir d'une image volumique reconstruite Download PDF

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WO2012085912A2
WO2012085912A2 PCT/IL2011/000957 IL2011000957W WO2012085912A2 WO 2012085912 A2 WO2012085912 A2 WO 2012085912A2 IL 2011000957 W IL2011000957 W IL 2011000957W WO 2012085912 A2 WO2012085912 A2 WO 2012085912A2
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bone
image
cylindrical
calculating
generating
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PCT/IL2011/000957
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WO2012085912A3 (fr
WO2012085912A9 (fr
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Elazar ZELZER
Tomer STERN
Amnon SHARIR
Ron SHAHAR
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Yeda Research And Development Co. Ltd.
Yissum Research Development Company Of The Hebrew University Of Jerusalem Ltd.
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Priority to EP11813573.0A priority Critical patent/EP2656306A2/fr
Priority to US13/995,989 priority patent/US20130272594A1/en
Publication of WO2012085912A2 publication Critical patent/WO2012085912A2/fr
Publication of WO2012085912A3 publication Critical patent/WO2012085912A3/fr
Publication of WO2012085912A9 publication Critical patent/WO2012085912A9/fr

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    • G—PHYSICS
    • G06—COMPUTING; CALCULATING OR COUNTING
    • G06T—IMAGE DATA PROCESSING OR GENERATION, IN GENERAL
    • G06T3/00—Geometric image transformations in the plane of the image
    • G06T3/06—Topological mapping of higher dimensional structures onto lower dimensional surfaces
    • G06T3/073—Transforming surfaces of revolution to planar images, e.g. cylindrical surfaces to planar images
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B6/00—Apparatus or devices for radiation diagnosis; Apparatus or devices for radiation diagnosis combined with radiation therapy equipment
    • A61B6/52—Devices using data or image processing specially adapted for radiation diagnosis
    • A61B6/5211—Devices using data or image processing specially adapted for radiation diagnosis involving processing of medical diagnostic data
    • G—PHYSICS
    • G06—COMPUTING; CALCULATING OR COUNTING
    • G06T—IMAGE DATA PROCESSING OR GENERATION, IN GENERAL
    • G06T11/00—2D [Two Dimensional] image generation
    • G06T11/003—Reconstruction from projections, e.g. tomography
    • G06T11/008—Specific post-processing after tomographic reconstruction, e.g. voxelisation, metal artifact correction
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B6/00—Apparatus or devices for radiation diagnosis; Apparatus or devices for radiation diagnosis combined with radiation therapy equipment
    • A61B6/54—Control of apparatus or devices for radiation diagnosis
    • A61B6/548—Remote control of the apparatus or devices

Definitions

  • the present invention in some embodiments thereof, relates to method and system of imaging and/or diagnosing a bone and, more particularly, but not exclusively, to a method and system of imaging and/or diagnosing a bone from a reconstructed volume image.
  • Bone disorders such as Osteoporosis, do not have a visible expression and therefore hard to detect and to evaluate accurately.
  • Various methods have been developed in the last years for imaging bone characteristics, such as density.
  • Bone mineral density is measured mainly through the use of x-ray based technologies such as dual energy x-ray absorptiometry (DXA or DEXA) and, to a lesser extent, quantitative computed tomography (QCT).
  • DXA and QCT techniques have many desirabie characteristics, such as high sensitivity to the morphology and mineralization of the bone, based on which the risk of fractures can be estimated.
  • Ultrasound also has been shown to be reliable in estimating bone mineral density and predicting the risk of fracture, and has the desirable characteristics of not involving ionizing radiation and using lower cost equipment.
  • small C-arm fluoroscopes or simply small C-arms, that typically are used for both surgery and diagnosis of extremities, but can be provided with the additional capability of making bone assessment measurements.
  • Hologic, Inc. of Bedford, Mass. offers a line of DXA equipment tinder the trade names ACCLAIM and ODR and model designations such as 4500 and 1000, an ultrasound bone sonometer under the trade name Sahara, and a small C-arm under the trade name Fluoroscan followed by model designations.
  • US Patent Application No 2002/0022779 describes a compact magnet and an RF probe which can accommodate a human extremity such as a heel are used to construct a compact MR.! system for diagnosis and follow-up of osteoporosis and other diseases.
  • Methods for measuring and calculating proton density in inhomogeneous static magnetic field, magnetic field gradients, and RF magnetic field are provided using 2D spin-echo image acquisitions with external reference materials and image analyses.
  • the measured proton density of bone marrow is used for computation of trabecular bone volume fraction, which can be used for diagnosis of osteoporosis and other diseases.
  • US Patent Application No. 2010/0142675 describes a method and system for determining the bone mineral density of a body extremity.
  • An image of a body extremity is acquired using a mammography x-ray system whereby a bone mineral density inspection can be performed on the image.
  • the system for determining the bone mineral density of a body extremity includes: a support for supporting the body extremity; a detector for capturing an image of the body extremity; and an x-ray source adapted to project an x-ray beam through the body extremity toward the detector, the x-ray source having a voltage of no more than about 45 kVp and having a target/filter combination of rhodium/rhodium, molybdenum/ molybdenum,
  • a method of imaging and/or diagnosing intrabony space comprises providing a reconstructed volume image depicting a cylindrical bone, identifying a segment depicting the cylindrical bone in the reconstructed volume image, transforming the segment to generate a three-dimensional (3D) model which aligns a representation of each of a plurality of radial portions having a plurality of different angular orientations of the cylindrical bone in parallel to a common axis, generating at least one coded image mapping of at least one osteo related characteristic of the cylindrical bone along each the radial axis, and outputting the at least one coded image and/or a numeral value quantifying one or more properties of the cylindrical bone.
  • 3D three-dimensional
  • the at least one coded image is color coded.
  • the outputting comprising presenting the at least one coded image.
  • the method further comprises analyzing the at least one coded image to automatically diagnose at least one osteo related pathology.
  • the method further comprises registering at least the segment onto a nonlinear cylindrical space, the transforming comprising mapping the plurality of radial portions by a transformation from the continuous nonlinear cylindrical space to a continuous Euclidean space.
  • the generating comprising calculating a bone mineral content (BMC) along each the radial portion.
  • BMC bone mineral content
  • the generating comprising calculating an unweighted bone mineral content (uwBMC) along each the radial portion.
  • uwBMC unweighted bone mineral content
  • the generating comprising calculating a bone mineral density (BMD) along each the radial portion.
  • BMD bone mineral density
  • the generating comprising calculating an unweighted bone mineral density (uwBMD) along each the radial portion.
  • uwBMD unweighted bone mineral density
  • the generating comprising calculating the distance from the center of the Bone marrow to the Endosteum (Endosteal thickness) along each the radial portion.
  • the generating comprising calculating the thickness of the Cortex
  • the generating comprising calculating the distance from the center of the Bone marrow to the Periosteum (Periosteal thickness) along each the radial portion.
  • the generating comprising calculating the fraction of volume that is not mineralized along each the radial portion, including only the part between the endosteum and the periosteum, referred to as Cortical Porosity.
  • Cortical Porosity the fraction of volume that is not mineralized along each the radial portion, including only the part between the endosteum and the periosteum.
  • the volume along the axis which includes marrow (no mineral) divided by the total volume along the axis (both with and without mineral) from the endosteum to the periosteum (i.e. without a portion from the center of the bone to the endosteum).
  • the generating comprising calculating the fraction of axis length that is not mineralized along each the radial portion, including only the part between the endosteum and the periosteum (referred to as unweighted Cortical Porosity).
  • the generating comprising calculating the at least one osteo related characteristic along each the radial axis as a function of a pluralit of radiodensity units of respective voxels in at least the segment.
  • the reconstructed volume image is obtained by a computed tomography (CT) scanning.
  • CT computed tomography
  • the at least one osteo related characteristic comprises morpho-density characteristics.
  • the method further comprises diagnosing an osteoporotic level of the cylindrical bone by analyzing the at least one coded image.
  • the method further comprises detecting at least one metastatic or primary tumor site in the cylindrical bone by analyzing the map.
  • the plurality of radial axes are perpendicular to a longitudinal axis of the cylindrical bone.
  • the transforming emulates the spreading of the corte layer of the segment on a plane.
  • the reconstructed volume image depicting a plurality of cylindrical bones the identifying, transforming, generating, and outputting are iterative!)' repeated with each the cylindrical bone.
  • a system of imaging intrabony space comprising an interface which receives a reconstructed volume image depicting a cylindrical bone, a computing unit which transforms a segment depicting the cylindrical bone in the reconstructed volume image to generate a three-dimensional (3D) model which aligns a representation of each of a plurality of radial axes having a plurality of different angular orientations of the cylindrical bone in parallel to a common axis and generates at least one coded image mapping of at least one osteo related characteristic of the cylindrical bone along each the radial axis, and a display which outputs the at least one coded image.
  • 3D three-dimensional
  • the interface receives the reconstructed volume image from a member of a group consisting of: a computer aided diaguosis (CAD) module, a client. terminal of a physician, a central database, a DICOM server, a radiology information system ( IS), a hospital information system (HIS), and a clinical information system (CIS).
  • CAD computer aided diaguosis
  • a client. terminal of a physician a central database
  • DICOM server a radiology information system
  • HIS hospital information system
  • CIS clinical information system
  • a method of diagnosing an intrabony space comprises providing at least one coded image mapping a sum of values of at least one osteo related characteristic in each of a plurality of portions of at least one bone of a patient, analyzing a pattern depicted in the at least one coded image to identify a pathological expression, and outputting an outcome of the analysis.
  • the sum is weighted.
  • the method further comprises calculating the osteo related characteristic per voxel in least one reconstructed volume image of the at least one bone, the osteo related characteristic is selected from a group consisting of a bone mineral content (BMC), an unweighted bone mineral content (uwBMC) a bone mineral density (BMD), an unweighted bone mineral density (uwBMD), a value for calculating a Cortical Thickness, a value for calculating Endosteal Thickness, a value for calculating Periosteal Thickness, a value for calculating Cortical Porosity, a value for calculating unweighted Cortical Porosity.
  • BMC bone mineral content
  • uwBMC unweighted bone mineral content
  • BMD bone mineral density
  • uwBMD unweighted bone mineral density
  • the analyzing comprises: selecting at least one 2D reference map according to at least one demographic characteristic of the patient, and matching between the at least one 2D reference map and the at least one coded image.
  • the at least one coded image comprises a plurality of coded images
  • the analyzin comprises matching between the plurality of coded images to identity a difference and performing the analysis according to the difference.
  • Implementation of the method and/or system of embodiments of the invention can involve performing or completing selected tasks manually, automatically, or a combination thereof. Moreover, according to actual instrumentation and equipment of embodiments of * the method and/or system of the invention, several selected tasks could be implemented by hardware, by software or by firmware or by combination thereof using an operating system .
  • a data processor such as a computing platform for executing a plurality of instructions.
  • the data processor includes a volatile memory for storing instructions and/or data and/or a non-volatile storage, for example, a magnetic hard-disk and/or removable media, for storing instructions and/or data.
  • a network connection is provided as well.
  • a display and/or a user input device such as a keyboard or mouse are optionally provided as well.
  • FIGs. 2A-2B are schematic illustrations of an exemplary cylindrical bone in pre transformed and transformed states, according to some embodiments of the present invention.
  • FIGs. 3A- 3B depict a cross section of a 3D segment of a bone depicted in a CT image and the cross section after having been transformed, generated according to some embodiments of the present, invention
  • FIG. 4 is a flowchart of a process for constructing a nonlinear cylindrical grid, according to some embodiments of the present invention.
  • FIG. 5A is a schematic illustration of exemplary unrolled image maps which are generated using different operators, from the bones shown in FIG. 5B, according to some embodiments of the present invention:
  • FIG. 5B is a schematic illustration of Ulna bones of a wild type (WT) mouse and a bone morphogenetic protein 2 (BMP2) conditional knockout (ICO.) mouse;
  • WT wild type
  • BMP2 bone morphogenetic protein 2
  • FIG. SC is a schematic illustration of other exemplary coded maps (images) of a Tibia bone having a BMP4 manipulated gene, which are generated using different operators, according to some embodiments of the present invention
  • FIG. 6 is a set of exemplary coded images, unrolled image maps, generated from two human Humeri bones of a healthy patient (left) and an Osteoporotic patient (right) which are indicative of BMD in the entire proximal ends ( ⁇ 3.5cm) of the bones, according to some embodiments of the present invention
  • FIGs. 7 A, 7B, and 7C depict additional exemplary coded images, unrolled image maps, of the same Humeri bones as in FIG. 6, which are generated using different operators, according to some embodiments of the present invention
  • FIGs. 8A-8C and FIGs. 9A-9C are coded images, unrolled image maps, of left and right femur bones of a health patient and a cancerous patient, generated according to some embodiments of the present invention.
  • FIG. 10 is a flowchart of a method of diagnosing an ntrabony space, according to some embodiments of the present invention.
  • FIG. I I is a schematic illustration of an imaging system of imaging intrabony space of a cylindrical bone, for example by implementing the method depicted in FIG.. I, according to some embodiments of the present invention.
  • the present invention in some embodiments thereof, relates to method and system of imaging and/or diagnosing a bone and, more particularly, but not exclusively, to a method and system of imaging and/or diagnosing a bone from a reconstructed volume image.
  • the osteo related characteristic may be a bone mineral content (BMC), a unweighted bone mineral content (uwBMC), a bone mineral density (BMD), an unweighted bone mineral density (uwBMD), the Cortical Thickness of the bone, and/or any other characteristics of the bone which may be extracted from the transformed 3D image.
  • the coded image is optionally extracted from a segment depicting a bone of a patient in a reconstructed volume image, such as a CT image.
  • the analysis is optionally performed by comparative analysis, which may be referred to herein as matching, between the pattern depicted in the coded image and a pattern depicted in a 2D reference map.
  • the 2D reference map is optionally selected from a database which includes a plurality of reference models, each depicts an exemplary pattern associated with a different demographic group of patients.
  • the demographic groups may be divided according to different age, gender, race, pathology, and/or medical condition.
  • the analysis of the coded image of the patient allows identifying local indicators in the different volumes of the depicted pattern.
  • a segment depicting a cylindrical bone in a reconstructed volume image such as a CT image
  • a three-dimensional (3D) model that aligns a representation of each of a plurality of radial portions, having a plurality of different angular orientations, of the imaged cylindrical bone in parallel to a common axis, for example from a regular Euclidean space
  • a Nonlinear-Cylindrical coordinate system on the Euclidean space i.e. on the pre-transformed image
  • representing the Nonlinear- Cylindrical coordinate system using a quasi-Euclidean space
  • a radial portion means a linear segment, which is one of some number of linear segments radiating from a longitudinal axis, linear, curved, or graded, of a bone, connecting the longitudinal axis with the bone surface or with some other point outside of the surface of the bone.
  • a method of imaging and/or diagnosing intrabony space that is based on such a reconstructed volume image that depicts a cylindrical bone.
  • the received reconstructed volume image is processes lo identify a segment that depicts the cylindrical bone in the reconstructed volume image.
  • the segmented bone is then transformed to a target space, such as Euclidean space where a plurality of radial axes of the imaged cylindrical bone are aligned in parallel to a common axis. This allows generating one or more maps which map the osteo related characteristics of the cylindrical bone along each radial axis and outputting these map(s) to a display and/or a processing unit.
  • Such maps allow manual and/or automatic diagnosis of a bone segment in a reconstructed volume image, which may be understood as an unsegmented image of a bone and a mask defining location, size, shape, and/or orientation the bone segment, and/or a portion thereof, for example for estimating the presence and/or absence of metastatic sites and/or osteoporotic level.
  • FIG. 1 is a flowchart 100 of a method 100 of imaging and/or analyzing intrabony space of cylindrical bones, according to some embodiments of the present invention.
  • the method 100 includes a transformation that is based on the morphology of the cylindrical bones, such as the Femur and the Tibia and/or cylindrical portions of bones, such as the Radius, the Ulna, the Humerus, the Femur, the Tibia, the Fibula, the ribs, and the like.
  • FIGs. 2A-2B are schematic illustrations of an exemplary cylindrical bone in pre transformed and transformed states, according to some embodiments of the present invention.
  • FIGs. 2A-2B are schematic illustrations of an exemplary cylindrical bone in pre transformed and transformed states, according to some embodiments of the present invention.
  • These figures figuratively illustrate a transformation by the method which may be performed by identifying and/or estimating a longitudinal central axis of a bone, optionally using a model or a volume center estimation in different cross sections, followed by performing a virtual cut on the cortex of the cylindrical bone along its entire length from a predefined angle, for example as shown at 151, referred to herein as a perspective angle, and unrolling the entire cortex of the bone from the cut, about the longitudinal central axis to obtain a coded image which is based on an image of an unrolled bone, for example as depicted in FIG. 2B.
  • a coded image which may be referred to as a coded map, is an image which is optionally coded according to the weighted sum of values of one or more osteo related characteristics of each of a plurality of portions of the imaged bone.
  • the coding is optionally in colors and/or hues, where each color or hue is selected according to the weighted sum of values of one or more osteo related characteristics of each of a plurality of portions of the imaged bone.
  • a coded image may also be coded in gray scale colors. Each color or hue represents a different value. Each value is based on a weighted sum of one or more osteo related characteristics of voxels of a portion of the imaged bone.
  • the coded image may be a topographic map wherein the depicted height represents a value.
  • the coded image may be a processed map wherein areas in which the weighted sum of values of one or more osteo related characteristics of is above a certain threshold level.
  • FIG. 2A and 2B A figurative image of an exemplary bone and an unrolled version of this exemplary bone are provided in FTGs. 2A and 2B.
  • this is a non limiting schematic example as the intrabony space may be imaged in various ways, as described below.
  • a reconstructed volume image having a three dimensional (3D) segment representing at least a portion of an intrabony space of one or more cylindrical bones is provided.
  • a reconstructed volume image means an image obtained by computed tomography (CT) scanning, an image obtained by magnetic, resonance imaging (MRI) scanning, an image obtained by posit on emission tomography (PET)-CT scanning, and/or any other medical scanning modality.
  • CT computed tomography
  • MRI magnetic, resonance imaging
  • PET posit on emission tomography
  • the 3D segment is optionally a set of voxels represented in the reconstructed volume image.
  • the 3D bone which is imaged in the provided reconstructed volume image is registered to a known spatial position i an Euclidean space.
  • the registration is performed by a pairwise/multiple image registration method.
  • a crude segmentation using a global threshold is applied in order to enable extraction of morphological bone features and better the distinction between bone and non-bone voxels.
  • circumferential features of the bone are extracted, based on which the initial approximation of the registration is performed.
  • several transformations are considered, and the one having the optimal score is taken for fine tuning.
  • a fine tuning step takes place based on a volume based registration module until convergence is reached to a desired level.
  • An optional way to generalize the method for multiple bones is by performing multiple pairwise alignments between all pairs of sufficiently similar bones, constructing a Minimum Spanning Tree from the obtained results based on .he scores of the pairwise registrations, and transforming each bone image based on its location on the spanning tree relatively to a predefined "root" image.
  • a cylindrical bone which is represented in the reconstructed volume image is segmented, referred to herein as a segmented bone.
  • the segmentation may be performed using known bone segmentation algorithms, for example see Y. Kang, K. Engclke, and W. A.lumina, "A new accurate and precise 3- D segmentation method for skeletal structures in volumetric CT data " IEEE Trans. Med. imag., vol. 22, no. 5, pp. 586-598, May 2003, V. Grau, U. U. J. Mewes, M. Alcaniz, R. Kikinis, and S. K. Warfieid. "Improved watershed transform for medical image segmentation using prior information," IEEE Trans. Med. Imag., vol.
  • a transformation which maps each coordinate of the bone segment into a coded image, optionally in a quasi-Euclidean target space.
  • the transformation constructs a nonlinear grid based on control points that are described below so that unsegmented and binary masks are transformed.
  • the transformation optionally defines a Nonlinear-Cylindrical coordinate system on the regular Euclidean space of the original CT image, and then represents the image in its Nonlinear- Cylindrical coordinate system based on a quasi-Euclidean space.
  • This transformation allows, as shown at 104, generating one or more coded images which are indicative of a value of one or more osteo related characteristics of each of a plurality of radial portions of the imaged bone.
  • a radial portion means a portion of the bone along a straight line between the main longitudinal axis of the bone and the outer surface of the corte and/or along a line which bisects or otherwise divides the body of the imaged bone.
  • a osteo related characteristic means a bone mineral content (BMC) along the radial portions of the bone, a bone mineral density (BMD) along the radial radial portions of the bone, the Cortical Thickness of the bone (as the distance from the Endosteum to the Periosteum of the bone), and/or any other characteristics of the depicted bone which may be extracted from the imaged bone segment.
  • Optional measuring units for density related characteristics are the Hounsfield Units (HU) and g cm ⁇ 3.
  • FIGs. 3A and 3B depict a 2D simplification (without considering the longitudinal axis) of the method with a single cross section of an embryonic day 18 Femur bone of a WT mouse (top) and the corresponding transformed section (bottom).
  • the transformation is carried out by setting a 2D polar coordinate system, defined by angular and radial axes with an origin superimposed on the geometric center of the putative region formerly occupying the cartilaginous model of the bone and marked by a dashed line 359.
  • the transformed slide, depicted in FIG. 3B may be obtained by representing the transversal slide, depicted i FIG.
  • the arrow 358 depicted in FIG. 3A is a radial portion having a length of 0.31 mm and an orientation of 35° from axis 0°. After having been transformed, the entire line of voxels lying about it (based on the nonlinear cylindrical coordinate system) is located perpendicularly to the 35° of the X axis, with length of 0.3.1mm.
  • 3B allows performing simple angle-wise calculations in a quasi- Euclidean space and imaging the cross section in an informative manner, emphasizing important morphological aspects, like the distance between the Periosteum of the bone and the geometric center of the cartilaginous model at each direction.
  • the obtained quasi-Euclidean space can be viewed as a data structure for simplifying the design and execution of complex calculations originally built for a non-linear cylindrical coordinate system by representing it using a simple 3D matrix.
  • the transformation is a R 3 ⁇ R 3 transformation that is optionally a deforming, yet reversible, information preserving, transformation, defined on 3D images of long bones and their binary masks as obtained from optionally a segmentation procedure.
  • the transformation is performed from the original Euclidean space on which a nonlinear cylindrical coordinate system is defined, to a quasi-Euclidean space representing the nonlinear cylindrical system.
  • l denotes a longitudinal/curvature axis
  • ⁇ denotes angular axis/azimuth
  • ⁇ denotes a radial axis.
  • the Nonlinear-Cylindrical coordinate system is optionally based on grid lines that determine the boundaries of non-cubic voxels that, assemble the Nonlinear-Cylindrical space. This also allows calculating the intensity and the volume/weight of each newly formed non-cubic voxel.
  • the transformation may be performed by assigning the resulting intensities and volumes into two regular 3D matrices (the quasi- Euclidean representation of the Nonlinear-Cylindrical system) indexed by (l, ⁇ , r ) > where one is for the intensities of the non-cubic voxels and the other is for the weight/volume of the non-cubic voxels.
  • the transformation is defined by the following algorithm:
  • receiving control points CP (cp 1 , ...,cp n ) where CP denotes a series of « 3D control points, sampled from the putative location of the longitudinal centre of the cartilaginous model prior its ossification (this is optionally done manually by an expert anatomists).
  • the order of the points along the length of the bone is from distal-most (cp 1 ) to proximal-most (cp n ); and receiving origin ⁇ ⁇ 1, ...,n) where origin denotes an index of the control point that marks the putative location of the anatomic origin of the entire diagnosed bone or diagnosed bone portion, for example the anatomic point around which the bone collar was formed;
  • a Polynomial Piecewise Function where the knot vector is defined to be: t - ⁇ ,-,, ⁇ .
  • C(l) denotes the point on the spline that, is I units from a point of an anatomic origin toward the proximal (distal) part of the bone if I is positive (negative), or for example the anatomic origin itself if I - 0, as measured by the ArcLength of C.
  • This parameterization provides a natural and an intuitive association betwee th anatomy of the bone and its mathematical representation.
  • the correspondence between I and t is inferred based on a function from I to t by taking a dense and uniformly spaced sample of values over the entire range of t, where 0 ⁇ dt « 1.
  • FIG. 4 is a flowchart, of a process tor constructing a nonlinear cylindrical grid, according to some embodiments of the present invention.
  • a single 2D polar coordinate system is established on a plane, which is normal to C(i) for each value of J, referred to herein as a normal plane from each point on C(f), where I € Z.
  • the single 2D polar coordinate system at a given point of C ⁇ 1) may be established by setting the origin at C ⁇ T) and constructing two orthogonal unit vectors, denoted herein as (0 and B(?) that serve as the 0 e and 90° axes, on the normal plane, respectively.
  • the pointing direction of the 0° axis which may be referred to as the primary axis, on the normal plane is now defined.
  • this definition is of where the cortex of the imaged bone and/or portion of the imaged bone is virtually cut to initiate the unrolling.
  • the pointing direction of the 90° axis which may be referred to as the perpendicular axis is set.
  • This setting defines the direction to which the bone is unrolled from the 0° axis, which may be referred to herein as a virtual cut, for example clockwise and/or counterclockwise, assuming a predefined convention.
  • the setting of these axes is done by a scheme in which the axes are not determined exclusively by the bone curvature (like in the Frenet-Serret formulas) but also according to the spatial position of the bone on the XYZ coordinate system.
  • all 0 ® axes are collinear with the XZ plane while pointing toward increasing X values, and the 90* axes point toward increasing Y values, assuming a relatively linear structure of the bone.
  • ⁇ CO and ®(D) are set to meet the following:
  • intermediate nonlinear cylindrical coordinate system may be defined as follows:
  • voxel oriented calculations are facilitated by defining the domain of the voxel V(l t 0 t r) as:
  • the volume, or an approximation thereof may be calculated for some or all of the voxels using a volume (triple) integral over the 3D domain.
  • an approximation may be calculated considering the volume of the
  • the intensity, or an approximation thereof, may be calculated for some or all of the voxels.
  • the interpolated is at ⁇ 1— 0.5, &— 0.5, r - OS) , yet to correspond with the described approximation of the volume, the value is optionally interpolated at the geometric center of the obtained convex hull using for example tnlineav interpolation or nearest-neighbor interpolation.
  • the relations between the continuous nonlinear cylindrical grid and the quasi-Euclidean space may be described as a shift between two 3D data representations, namely from a Nonlinear-Cylindrical coordinate system that the algorithm constructs uniquely for the specific bone within the original image - on which calculations may be very complicated, to a quasi-Euclidean space, where the originally curved curvature line of a cross section of the imaged bone is linearized to form the new Y axis, the circular/angular axes of the bone are linearized to fonn the new X axis, and the radial axes of the bone, each between the central axis and a point at a specific angle along the curvature line, form the new depth axis - Z, on which calculations (as will be demonstrated) can be made immeasurabl simpler.
  • the encircling surface of the imaged bone or portion which may be understood as a 360° envelope, internal -most to external-most faces the point of view of the user, while the voxels which depict the rest of the cortical wall and are followed by the voxels which depict the trabeculae and the marrow, if they are visible in the processed reconstructed volume image, reside deeper along the Z axis, figuratively behind the surface as shown at FIG. 2B (see region above the 360°).
  • the coded image which is optionally based on a transformed image of the unsegmented input image, which may be referred to herein as an unrolled bone image and optionally defined by the quasi-Euclidean space, is analyzed to extract one or more osteo related characteristics, such as morpho-density characteristics, of the imaged bone.
  • the one or more osteo related characteristics such as morpho-density characteristics
  • one or more mathematical operators are applied on the data in the unrolled bone image, for example in order to study the osteo related characteristics of one or more of the medullary cavity, the cortex, the endosteum, and/or the periosteum, along the radial axes of the imaged bone, for example the thickness and/or the density thereof.
  • the operators enable calculating and imaging information which is optionally associated with the distances between anatomically meaningful landmarks and/or density along the radial portions, while combining the information in some way. to form composite parameters.
  • one or more of the following osteo related characteristics each of the radial portions of the transformed bone, in different angles from the main longitudinal axis, are extracted using designated operators.
  • ⁇ ⁇ R*** * denotes a weight matrix where r— (l,...»r) and ⁇ , ⁇ , ⁇ ) denotes voxel dimensions in a pre-transformation image /.
  • Each operator returns an unrolled image map, which is a 2D matrixe
  • WMCil ⁇ ] dv* ⁇ r U ⁇ 1, ⁇ , ⁇ 1 7 ⁇ , rj.
  • Unweighted Bone Mineral Content - based on an unweighted bone mineral content.
  • Periosteal thickness - based on a map showing the distances of the Periosteum from the curvature line: Tktck p rt ⁇ lj, 0 ⁇ - dv SrW ⁇ J ⁇ r].
  • Cortical thickness - based on a map showing the thickness of the cortex (from Endosteum to Periosteum): Th£ck e ⁇ >rt U> 0] hld ⁇ l 9] - Thick ⁇ ndi> [l 9] .
  • One of the advantages of analyzing the data in the unrolled image is that the relatively planar representation of the bone enables to calculate numerous mineralization and morphological characteristics at each sectional segment of the entire bone in a straightforward calculation and/or to visualize the results as 2D topographic maps. This allows detecting minute phenotypic alterations caused by a genetic origin and/or an environmental origin.
  • FIG. 5A depicts exemplary coded images, also referred to as unrolled image maps, which are generated using different operators, for example as described above, according to some embodiments of the present invention.
  • FIG. 5A depicts unrolled image maps which are based on unrolled images of the Ulna bones of a wild type (WT) mouse and a bone morphogenetic protein 2 (BMP2) conditional knockout (K.O.) mouse at embryonic day 17, such as the bones depicted in FIG. 5B.
  • BMPs are a group of growth factors which are known for their ability to induce ectopic bone formation.
  • BMPs are also known to participate in the process of bone development. The molecular mechanisms by which BMPs act and their influence on the general morphology and mineralization of developing bones is still not fully understood.
  • the right side unrolled image maps are based on an unrolled image of an imaged bone of a transgenic mouse with inactivated BMP2 expressions in a limb- specific manner prior to the onset of skeletal development, referred to herein as BMP2 bone.
  • the left side unrolled image maps are based on an unrolled image of an imaged bone of a WT mouse, referred to herein as WT bone.
  • the unrolled image maps explicitly depict significant differences:
  • the BMC of the WT bone is significantly higher in most of its sectional regions than in respective sectional regions of the BMP2 bone.
  • the BMD of the WT bone is significantly lower in a significant portion of its sectional regions than in respective sectional regions of the BMP2 bone.
  • BMD - in red The spread of high density regions (BMD - in red) is relatively scattered in the WT bone, where in the BMP2 bone it lends to aggregate in two primary regions.
  • the coded images depicted in FIG. 5A show the influence of the BMP2 gene on the morphology, the mineral density, and the spatial organization of mineral in embryonic bones. This indicates that. BMP2 has a role in skeletal patterning. It should be noted that in 2006 a group of researchers from Harvard University has published a letter in Nature Genetics [19], describing the results of a study performed on BMP2, in which transgenic mice with inactivated BMP2 expression in a limb-specific manner prior to the onset of skeletal development, have been tested for their potential to initiate an endogenous bone repair response after having been fractured.
  • BMP4 is a member of the previously described BMP group.
  • a transgenic mouse with inactivated expression of the BMP4 gene in a limb-specific manner prior to the onset of skeletal development will result in the absence of important skeletal elements like the Deltoid Tuberosity of the Humerus bone and the Lesser Trochanter of the Femur bone, yet no influence of BMP4 on the general morphology or mineralization of the developing bone has been reported so far.
  • the coded images depicted i FIG. 5C show the influence of a complete conditional K.O.
  • BMP4 Bone Morphogenetic Protein
  • the BMD is somehow increased in conditional K.O. mouse, and while in WT mouse there are quite a few "mineral holes" in which no mineral exists at all (color-coded black points scattered mostly on the left side of the map), almost no such holes are evident in the map of the conditional K.O. mouse.
  • BMC is significantly increased in the conditional K.O. mouse, especially around the right mid section of the map.
  • Cortical Thickness the estimated distance between periosteum and the
  • endosteum of the bone is significantly increased in conditional K.O. mouse, especially around the right mid section of the map.
  • the Cortical Radius of the bone (distance from the center of the marrow to the periosteum) is significantly increased in the conditional K.O. mouse, meaning that the conditional K.O. bone is much wider than the WT bone. 5. As can be seen in all the images, by the distance between the upper ends of the maps and the lower ends (the fraction of Y axis segment that is occupied by the maps), the conditional K.O. bone is longer than the WT bone.
  • conditional heterozygous bone presents phenotypes that from a visual inspection, suggest higher similarity to the conditional K.O. mouse than to the WT mouse.
  • the osteoporotic level of a Human bone may be diagnosed according to one or more of the generated coded images.
  • FIG. 6, is a set of two exemplary unrolled image maps which are indicative of BMD, generated as described above, according to some embodiments of the present invention.
  • the left and right unrolled image maps are based on an unrolled image generated from an image of a bone segment that is located at the first 3.5cm of the proximal side of a Human Humerus bone.
  • the left unrolled image map is based on an unrolled image of a bone segment of a 2.1 years old male (left) and the right unrolled image map is based on an unrolled image of a bone segment of an osteoporotic (OP) 83 years female.
  • FIG. 6 depicts a color-bar which indicates the correlation between the radio-density in Hounsfieid scale and the used colors.
  • the normal Humerus presents significantly higher overall levels of BMD than the OP Humerus, in addition, a closer look at the localized level between the normal and the OP bone reveals a negative correlation between the densities.
  • FIGs. 7A, 7B, and 7C depict exemplary unrolled image maps which are generated using different operators, according to some embodiments of the present invention.
  • FIG. 7A depicts the BMC, in HU scale, in normal and OP bones.
  • the unrolled image maps may be used tor diagnosing and studying osteo related pathologies in the bone segment.
  • the diagnosis may be performed manually, for example by a user which reviews a print or a display of the unrolled image maps and/or automatically by a computing unit which process the unrolled image maps.
  • the diagnosis is based on a comparison between respective organs, for example between left and right bones and/or different segments of a diagnosed bone.
  • the diagnosis is based on a comparison between the unrolled image map of the diagnosed bone and exemplary unrolled image maps which are generated from one or more exemplary bones, healthy and/or pathological.
  • the exemplary unrolled image maps may be based on a statistical analysis of a plurality of unrolled image maps of exemplary bones, optionally of patients having common characteristics, such as age, race, gender, weight, pathology, medical history and the like.
  • the unrolled image maps are diagnosed tor detecting the presence and/or the absence of one or more metastatic sites or primary tumors.
  • FIGs. 8A-8C and 9A-9C are unrolled image maps of left and right femur bones of a healthy patient and a cancerous patient, generated according to some embodiments of the present invention.
  • Each one of these figures also includes a map that indicates the differences between the mapped osteo related characteristics in respective radial axes of the left and right, femur bones.
  • FIGs. 8A and 9A depict unrolled image maps indicative of BMD in the femur bones.
  • FIGs. 8B and 9B depict unrolled image maps indicative of BMC in the femur bones.
  • FIGs. 8C and 9C depict unrolled image maps indicative of cortical thickness in the femur bones.
  • the difference between the respective osteo related characteristics in the left and right femur bones is relatively minor in all their radial axes.
  • the difference between the respective osteo related characteristics at the metastasis area is relatively high.
  • the differences between the BMD values of radial axes of the left femur bone and the right femur bone are relatively high.
  • the BMD values of the right femur bone, which is cancerous, are higher.
  • the rest of the infected bone has a much higher BMD level at non-metastatic regions than the normal bone.
  • This difference may be a normal reaction of the body to the presence of the metastasis and/or an outcome of a change in die posture and/or walking pattern of the patient.
  • the process depicted in 102-105 may be repeated a plurality of time for all the cylindrical bones which are depicted in the received reconstructed x'olume image.
  • a 3D image such as a CT image, for instance in a digital imaging and communications in medicine (DICOM) object, are analyzed.
  • DICOM digital imaging and communications in medicine
  • the process depicted i FIG- 1 and the aforementioned automatic diagnosis may be performed automatically on reconstructed volume images, such as CT images, providing the physician and/or the radiologist and additional indication about the pathological state of the imaged bones.
  • the process may be implemented by a computer aided diagnosis (CAD) module that process reconstructed volume images, such as CT images, for example on a client terminal of a physician and/or a radiologist and/or on images stored in a central database, such as a DICOM sewer, a radiology information system (RIS), and a hospital information system (HIS), also known as a clinical information system (CIS).
  • CAD computer aided diagnosis
  • the unrolled image maps may be used to quantify and/or image the properties of one or more metastatic sites or primary tumors which identified therein and serve for staging the patient, for follow-ups during treatments, and for the identification of otherwise hardly visible instances of the disease.
  • This platform may serve any bone related clinical situation that is evident in mineralization or morphology, other examples: skeletal traumas, Osteomalacia, Osteogenesis Imperfecta, and the like.
  • FIG. 10 is a flowchart 700 of a method of diagnosing an intrabony space, according to some embodiments of the present invention.
  • one or more coded images each of one or more rabody osteo related characteristics of one or more bones of patient are provided.
  • Each coded image is optionally generated as described above with reference to FIG. I.
  • the osteo related characteristic may be a BMC, a BMD, the Cortical Thickness of the bone, and/or any other characteristics of the bone which may be extracted from the coded image, for example as described above.
  • the coded image is optionally extracted from a segment depicting a bone of a patient in a reconstructed volume image, such as a CT image, for example as described above.
  • the one or more coded images are analyzed to identify in each one or more pathological expressions in patterns depicted in the coded image(s) and/or one or more local pathological indicators.
  • the analysis is optionally performed, in each coded image, by matching between the pattern depicted in the coded image and a pattern depicted in a 3D reference map.
  • the 3D reference map is optionally selected from a database which includes a plurality of reference models, as shown at 703.
  • Each reference model depicts an exemplar pattern associated with a different demographic group of patients.
  • the demographic groups may be divided according to different age, gender, race, pathology, and/or medical condition.
  • the analysis of the coded image of the patient allows identifying local indicators in the different, volumes of the depicted pattern.
  • FIGs. 9A- C depicts a local indicator (encircled area) that is indicative of cancer.
  • Such local indicators which are optionally pathological expression of the one or more osteo related characteristics in different volumes of the depicted pattern, are very unlikely to be identified by summing data from the bone as a whole. The summing of data from the bone as a whole, for example by averaging, does not. reflect, pathological expressions in different volumes of the bone and does not allow detecting a pathology which has a local expression which is not reflected most of the intrabony space.
  • the pattern depicted in the coded image may be analyzed to identify pathologies which have different expressions i different intrabony volumes. For example, as depicted in FIG.
  • BMP2 may be identified by high MD spots in specific areas of the bone.
  • Such expressions which are optionally pathological expressions of the one or more osteo related characteristics in the depicted pattern, ar either unlikely or impossible to be identified by summing data from the bone as a whole.
  • the summing of data from the bone as a whole for example by averaging, ignores the pattern and as it relates only a sum of values and does not allow detecting a pathology which has a pattern not reflected by values of voxels from an image depicting the. intrabony space.
  • two coded images are separately generated for respective segments in respective left and right bones, for example as shown at FIGs. 8A-8C and 9A-9C.
  • patterns from the two coded images may be compared to allow identifying identity, similarity, and/or variation therebetween.
  • FIGs. 9A-9C depicts a repetition of the same local indicator in each of the two coded images.
  • the outcome of the analysis is outputled, for example displayed to a clinician on a display connected to a local client terminal, a thin terminal, and/or any other computing device.
  • the outcome may also be documented in a medical database, such as PACS, RIS, CIS and/or HIS, optionally as another record of the patient, for example in association with a reconstructed volume from which the coded image is extracted.
  • FIG. 1.1 is a schematic illustration of an imaging system 401 of imaging intrabony space of a cylindrical bone, for example by implementing the method depicted in FIG.l, according to some embodiments of the present invention.
  • the system 100 is optionally implemented on a network node, such as one or more servers and/or on a client terminal, such as a laptop, a tablet, a personal computer and the like.
  • the system 401 includes a computing unit 403 which executes one or more software applications and/or modules, referred to herei as a transformation module 405 for calculating the visualization of the intrabony space, as described above, and to generate one or more maps of osteo related characteristics accordingly.
  • the computing unit 403 comprises and/or connected to a memory 404 which is set to store the respective .software applications and/or modules.
  • the system includes an interface 402 which receives a reconstructed volume image depicting a cylindrical bone, for example as described bone.
  • the interface is optionally a network interface for receiving the image via to a computer network, such as a local area network (LAN) and/or a wide area network (WAN).
  • the network interface 402 optionally comprises a wireless network interface controller (WNIC) which connects to a radio-based computer network, optionally based on IEEE 802.1.1 standards.
  • WNIC wireless network interface controller
  • the network interface 402 optionally comprises a network interface controller (NIC) which connects to a wire-based network such as token ring or Ethernet.
  • NIC network interface controller
  • the computing unit 403 transforms a segment depictin the cylindrical bone in the reconstructed volume image to generate a 3D model which aligns a representation of each of a plurality of radial axes having a plurality of different angular orientations of the cylindrical bone in parallel to a common axis, for example by performing a transformation as described above and depicted in FIGs. 2A and 2 .
  • the computing unit 403 generates maps which map osteo related characteristics) of the cylindrical bone along various radial axes as described above.
  • the system 401 further includes a display 404 which presents the maps, for example an LCD monitor and/or a projector.
  • the interface 402 receives reconstructed volume image from a central database as described above.
  • diagnosis may refer to the act of "bone analysis”.
  • composition or method may include additional ingredients and/or steps, but only if the additional ingredients and/or steps do not materially alter the basic and novel characteristics of the claimed composition or method.
  • a compound or “at least one compound” may include a plurality of compounds, including mixtures thereof.
  • range format is merely for convenience and brevity and should not be construed as an inflexible limitation on the scope of the invention. Accordingly, the description of a range should be considered to have specifically disclosed ail the possible subranges as well as individual numerical values within that range. For example, description of a range such as from 1 to 6 should be considered to have specifically disclosed subranges such as from 1 to 3, from to 4, from 1 to 5, from 2 to 4, from 2 to 6, from 3 to 6 etc., as well as individual numbers within that range, for example, I, 2, 3, 4, 5, and 6. This applies regardless of the breadth of the range.

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Abstract

La présente invention concerne un procédé d'imagerie d'un espace interosseux ou de diagnostic de l'état dudit espace interosseux. Le procédé comprend la fourniture d'une image volumique reconstruite représentant un os cylindrique, l'identification d'un segment représentant l'os cylindrique sur l'image volumique reconstruite, la transformation du segment pour générer un modèle en trois dimensions (3D) qui aligne une présentation de chacune d'une pluralité de parties radiales ayant une pluralité de différentes orientations angulaires de l'os cylindrique parallèlement à un axe commun, la génération du mappage d'au moins une image codée d'au moins une caractéristique liée à l'os de l'os cylindrique le long de l'axe radial, et l'impression de la ou des images codées.
PCT/IL2011/000957 2010-12-21 2011-12-21 Procédé et système d'imagerie d'un os et/ou de diagnostic de l'état d'un os à partir d'une image volumique reconstruite WO2012085912A2 (fr)

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